Diet influences the functions of the human intestinal microbiome

Gut microbes programme their metabolism to suit intestinal conditions and convert dietary components into a panel of small molecules that ultimately affect host physiology. To unveil what is behind the effects of key dietary components on microbial functions and the way they modulate host-microbe interaction, we used for the first time a multi-omic approach that goes behind the mere gut phylogenetic composition and provides an overall picture of the functional repertoire in 27 fecal samples from omnivorous, vegan and vegetarian volunteers. Based on our data, vegan and vegetarian diets were associated to the highest abundance of microbial genes/proteins responsible for cell motility, carbohydrate- and protein-hydrolyzing enzymes, transport systems and the synthesis of essential amino acids and vitamins. A positive correlation was observed when intake of fiber and the relative fecal abundance of flagellin were compared. Microbial cells and flagellin extracted from fecal samples of 61 healthy donors modulated the viability of the human (HT29) colon carcinoma cells and the host response through the stimulation of the expression of Toll-like receptor 5, lectin RegIIIα and three interleukins (IL-8, IL-22 and IL-23). Our findings concretize a further and relevant milestone on how the diet may prevent/mitigate disease risk. Introduction Comprising 1012-14 cells from 100 -1000 species, the human intestinal microbiome is a complex entity living in our body. It affects human health, sustenance and well-being1. Functioning as an extra organ2, the intestinal microbiome uses nutrients from ingested foods, releases harmful or beneficial metabolites and regulates the immune system3,4. Dysbiosis of the intestinal microbiome has been associated to various gastrointestinal (GI) and non-GI diseases, such as obesity, heart-, kidney- and liver-related diseases, cancer and autism5,6,7, but the dilemma whether it acts as cause or consequence remains too far from the solution. Because the simple phylogenetic characterization does not provide deep information on functional repertoires8,9, a number of projects and studies have employed the whole-community shotgun sequencing to combine the composition and gene content of the human intestinal microbiome2,10. Current meta-genomic data show limited differences among individuals, which hypothesize the existence of a stable core microbiome and similar metabolic traits10. Notwithstanding the relevance of these findings, they do not necessarily imply similar in vivo microbial activities. Indeed, a panel of factors (e.g., diet, host genetics and pharmacological treatments) markedly affect such activities11. Dietary components have the capability to modulate the composition and mainly the function of the intestinal microbiome3,12,13. Correlations between entero-gradients/types and vegetable-rich (Prevotella and Lachnospira) or animal protein-rich diets (Bacteroides and Clostridia/Ruminococcus) have been already highlighted12,14, but the impact of dietary components still remains unclear. Previously, we have determined the compositional structure of the fecal microbiota and metabolome of 150 healthy omnivorous, vegan and vegetarian volunteers, demonstrating that vegetable-rich foods increased both the abundance of fiber-degrading bacteria and the synthesis fecal short-chain fatty acids (SCFAs)14. In contrast, omnivorous volunteers having low adherence to the Mediterranean diet (MD) had the highest levels of detrimental microbial metabolites, such as phenolic and indole derivatives, and trimethylamine N-oxide (TMAO). This emerging picture hypothesizes that diet modulates the functionality of the intestinal microbiome, which, in turn, affects the human metabolic status15,16. In this study, we implemented a multi-omic approach (meta-genomic, -proteomic and -metabolomics) to thoroughly characterize fecal samples from omnivorous, vegan and vegetarian volunteers with the aim of showing the molecular relationship between diet and metabolic functions of the intestinal microbiome. We sought to identify the effects of key dietary components on microbial functions that modulate host-microbe interactions. This approach might lead to effective intervention strategies for maintaining human health via the diet-microbiome axis. Full-Article - Scientific Reports https://www.nature.com/articles/s41598-020-61192-y